Department of Pharmacy, China-Japan Friendship Hospital.
Faculty of Pharmaceutical Sciences, Mukogawa Women's University.
Chem Pharm Bull (Tokyo). 2023;71(7):520-527. doi: 10.1248/cpb.c22-00747.
Itraconazole, a commonly used antifungal drug in the clinic approved by U.S. Food and Drug Administration (FDA), has been gradually found to have anti-tumor, angiogenesis inhibition and other pharmacological activities. However, its poor water solubility and potential toxicity limited its clinical application. In order to improve the water solubility and reduce the side effects caused by the high concentration of itraconazole, a novel preparation method of itraconazole sustained release microspheres was established in this study. Firstly, five kinds of polylactic acid-glycolic acid (PLGA) microspheres loaded with itraconazole were prepared by oil/water (O/W) emulsion solvent evaporation and then characterized by infrared spectroscopy. Then the particle size and morphology of the microspheres were observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). After that, the particle size distribution, drug loading rate, entrapment efficiency, and drug release experiments were evaluated. Our results showed the microspheres prepared in this study had uniform particle size distribution and good integrity. Further study found that the average drug loading of the five kinds of microspheres prepared with PLGA 7505, PLGA 7510, PLGA 7520, PLGA 5020 and PLGA 0020 were 16.88, 17.72, 16.72, 16.57, and 16.64%, respectively, and the encapsulation rate all reached about 100%. More surprisingly, the release experimental results showed that the microspheres prepared with PLGA 7520 did not show sudden release, showing good sustained release performance and high drug release rate. To sum up, this study optimized the preparation method of sustained-release microspheres without sudden release, which provides a new solution for the delivery of itraconazole in the clinic.
伊曲康唑是美国食品和药物管理局（FDA）批准的临床常用抗真菌药物，逐渐发现其具有抗肿瘤、抑制血管生成等药理活性。但其水溶性差，潜在毒性限制了其临床应用。为提高伊曲康唑的水溶性，降低其高浓度引起的副作用，本研究建立了伊曲康唑缓释微球的新型制备方法。首先，采用油包水（O/W）乳液溶剂蒸发法制备了 5 种载伊曲康唑的聚乳酸-羟基乙酸（PLGA）微球，并通过红外光谱进行了表征。然后通过扫描电子显微镜（SEM）和透射电子显微镜（TEM）观察微球的粒径和形态。之后，对微球的粒径分布、载药量、包封率和药物释放实验进行了评价。结果表明，本研究制备的微球粒径分布均匀，完整性好。进一步研究发现，用 PLGA7505、PLGA7510、PLGA7520、PLGA5020 和 PLGA0020 制备的 5 种微球的平均载药量分别为 16.88%、17.72%、16.72%、16.57%和 16.64%，包封率均达到 100%左右。更令人惊讶的是，释放实验结果表明，用 PLGA7520 制备的微球没有突释现象，表现出良好的缓释性能和较高的药物释放率。综上所述，本研究优化了无突释的缓释微球的制备方法，为伊曲康唑在临床上的应用提供了新的解决方案。
